While MHC-restricted T helper cell interactions with macrophages and B cells have been well documented in recent years, very little is known about T-T cell interactions between T cell subpopulations. Recently, we isolated and characterized several self-Ia reactive (autoreactive) Lyt 1+2-,L3T4+, Ia-T cell clones from normal, unimmunized DBA/2 mice and used them to analyze the T - T network concept postulated to exist in the normal immune system. These studies led to an interesting and unique finding that Lyt 1+ but not Lyt 2+ T cells isolated from normal DBA/2 mice proliferate strongly and directly in response to autoreactive T cells. Further studies will be carried out to address the following specific aims: 1) Nature and characteristics of the T - T interaction between antiautoreactive Lyt 1+2- T cells and autoreactive T cells. 2) Do antiautoreactive Lyt 1+2-T cells have receptors with internal images of Ia molecules? 3) What is the functional significance of the T-T interaction and possible role of T cells bearing internal images of Ia on their receptors, in the generation of T-helper cell repertoire? The above mentioned studies will be carried out by using autoreactive T cell clones and hybridomas which have been developed and well characterized. Similar attempts will be made to develop anti-autoreactive Lyt1+2-T cell clones and hybridomas. Attempts will be made to develop mAbs to the autoreactive T cells and determine the nature of antigenic determinant recognized by the Lyt 1+2-T cells. Monoclonal antibodies will also be developed against the antiautoreactive T cell receptor and these along with mAbs to autoreactive T cells will be used in vitro and in vivo to understand the functional significance of the T-T interaction and its relation to the generation of the T-helper cell repertoire. It has been suggested that autoreactive T cells and T cell immune networks play an important role in maintaining normal immune system homeostasis and any perturbation in these cells could lead to disturbed immunoregulation and development of autoimmune or lymphoproliferative diseases and neoplasia. Thus, the present investigation would help in understanding the network regulation among T cells and its role in autoimmune or lymphopoliferative disorders and in neoplasia.